Exp Mol Med.  2009 Mar;41(3):133-139. 10.3858/emm.2009.41.3.016.

Tie2 is tied at the cell-cell contacts and to extracellular matrix by Angiopoietin-1

• Fukuhara S
• Sako K
• Noda K
• Nagao K
• Miura K
• Mochizuki

• KMID: 1123460
• DOI: http://doi.org/10.3858/emm.2009.41.3.016

Abstract

Angiopoietin-1 (Ang1) binds to and activates Tie2 receptor tyrosine kinase. Ang1-Tie2 signal has been proposed to exhibit two opposite roles in the controlling blood vessels. One is vascular stabilization and the other is vascular angiogenesis. There has been no answer to the question as to how Tie2 induces two opposite responses to the same ligand. Our group and Dr. Alitalo's group have demonstrated that trans-associated Tie2 at cell-cell contacts and extracellular matrix (ECM)-anchored Tie2 play distinct roles in the endothelial cells. The complex formation depends on the presence or absence of cell-cell adhesion. Here, we review how Ang1-Tie2 signal regulates vascular maintenance and angiogenesis. We further point to the unanswered questions that must be clarified to extend our knowledge of vascular biology and to progress basic knowledge to the treatment of the diseases in which Ang1-Tie2-mediated signal is central.

Keyword

angiopoietin-1; angiostatic proteins; cell movement; cell proliferation; extracellular signal-regulated MAP kinases; neovacularizaton, pathologic; neovascularization, physiologic; proto-oncogene proteins c-akt; receptor, TIE-2

MeSH Terms

Angiopoietin-1/*physiology
Animals
Cell Adhesion/physiology
Cell Movement/physiology
Endothelial Cells/*physiology
Endothelium, Vascular/physiology
Extracellular Matrix/*metabolism
Humans
Neovascularization, Physiologic/physiology
Receptor, TIE-2/*physiology
Signal Transduction/*physiology